Ichthyosis, Sjögren Larsson Syndrome

NORD gratefully acknowledges the members of the Medical and Scientific Advisory Board of the Foundation for Ichthyosis & Related Skin Types for assistance in the preparation of this report.

Synonyms of Ichthyosis, Sjögren Larsson Syndrome

Ichthyosis, Spastic Neurologic Disorder, Mental Retardation

SLS

General Discussion

Sjögren-Larsson syndrome is an inherited disorder characterized by scaling skin (ichthyosis), mental retardation, speech abnormalities, and spasticity. Affected infants develop various degrees of reddened skin with fine scales soon after birth. After infancy, the skin loses its redness and dark scales often appear on the neck and under the arms. Additionally, larger plate-like thick scales may develop on the lower legs. Developmental delay, speech abnormalities and seizures may accompany skin symptoms. Spasticity in the legs typically impairs motor ability and walking. Many children with this disorder have glistening white dots or degeneration of the pigment in the retina of the eye.

Signs & Symptoms

Symptoms of Sjögren-Larsson syndrome are usually evident at birth or during early infancy. This disorder is characterized by thickening of the skin (hyperkeratosis) with fine dry scales on most of the body associated with varying degrees of redness. After infancy, the flexural side of the arms and legs are affected by dark, scaly areas without redness.

In time, larger plate-like scales may appear on the skin’s surface, particularly on the legs. The skin has an itchy characteristic. Speech abnormalities, mental retardation and seizures usually occur during the first 2 or 3 years of life. Glistening white dots in the back portion of the inside of the eyeball (retina) may be a specific sign of the disorder.

Patients with Sjögren-Larsson syndrome typically develop some degree of leg spasticity, resulting in difficulty walking or an inability to walk. Less commonly, patients have short stature, and curvature of the spine.

Causes

Patients with Sjögren-Larsson syndrome have a deficient activity of fatty aldehyde dehydrogenase (FALDH) and are unable to metabolize a certain type of fat called “fatty alcohol.” Normally, fatty alcohol metabolism is important in the skin and brain, where it is used for the synthesis of membrane components.

Sjögren-Larsson syndrome is caused by mutations in the FALDH gene on the short arm of chromosome 17 (17p11.2). It is an inherited disorder transmitted in an autosomal recessive manner.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 17p11.2″ refers to a location on band 11 on the short arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

In recessive disorders the condition appears when the person inherits the same defective gene for the same trait from each parent. If the individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but will not show the condition. The risk of transmitting the disease to the children of a couple, both of whom are carriers for the recessive disorder, is approximately 25 percent per pregnancy.

Affected Populations

Sjögren-Larsson syndrome is a rare inherited disorder occurring in approximately 8.3 out of 100,000 persons in northern Sweden. It is less prevalent in the U.S. The disorder affects males and females in equal numbers.

Related Disorders

Symptoms of the following disorders may be similar to those of Sjögren-Larsson syndrome. Comparisons can be useful for a differential diagnosis.

Ichthyoses or “disorders of cornification” are general terms describing a group of scaly skin disorders. They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin. The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of the skin cells known as “corneocytes” or the fat-rich matrix around these cells. These cells can be thought of as bricks, while the matrix would be the mortar holding these cells together. (See “Ichthyosis” in the Rare Disease Database.)

Ichthyosis congenita (collodion baby; congenital ichthyosiform erythroderma; xeroderma; desquamation of the newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red, dry, and rough skin with large coarse and fine white scales. Itchiness (pruritus) usually also develops. Skin on the palms of the hands and soles of the feet can be abnormally thick. (For more information, choose “Ichthyosis Congenita” as your search term in the Rare Disease Database.)

Standard Therapies

The skin symptoms of Sjögren-Larsson syndrome can be treated by applying skin softening emollients. This can be especially effective after bathing while the skin is still moist. Lotions containing alpha-hydroxy acids can also be an effective treatment for the skin symptoms of this disorder. Anti-convulsant medication may control seizures. Physical therapy, speech therapy and special education services may be helpful.

Dietary restriction of fat (long chain fatty acids) and supplementation of medium chain fatty acids (triglycerides) has been associated with marked improvement in the skin symptoms in a few patients. In other patients, however, there has been no clinical response to dietary treatment.

Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.

If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

Representatives of patient organizations whose medical advisors are interested in assisting NORD in creating a report on a disease not currently covered in this database may write to orphan@rarediseases.org.